Glial scar formation, or fibrillary gliosis, a common pathological reaction of the central nervous system, accompanies a large, and varied, group of CNS disorders. These include CNS trauma, ischemic disease, demyelinating disorders, neuronal degenerative diseases, and metabolic storage diseases. Despite the fact that the histological changes of gliosis have been well-known for many years, little is understood of either the cellular and biochemical events underlying astrocyte reactions, or of the stimuli which provoke them. The proposed research is designed to explore cellular and biochemical mechanisms of fibrillary gliosis in both tissue culture systems of astrocytes and in lesions produced in situ. The initial studies will develop a primary cell culture system composed of astrocytes from rat CNS. Cultures will be used to study the synthesis and metabolism of the glial fibrillary acidic protein (GFAP), the subunit of intermediate filaments of astrocytes and the major protein component of CNS scar tissue. These studies will provide the necessary background for later investigations into pathophysiological stimuli that provoke fibrillogenesis or astrocyte proliferation. Experiments will explore the effects of such possible stimuli as serum factors, components of CNS tissues, and products of inflammatory cells on proliferation of cultured glia and on patterns of protein synthesis, in particular, of GFAP. In situ studies, examining the accumulation of GFAP during fibrillary gliosis following traumatic lesions in rat CNS, are also described. Cell cultures, radioisotope labeling, polyacrylamide gel electrophoresis, and procedures for isolating cytoskeletal elements of cells will be employed.